The sense of smell contributes to quality of life and warns of dangers present in the environment. Disease and injury that compromise this sensory modality decreases awareness of the outside world and puts one's life at risk. The olfactory epithelium (OE) is directly exposed to environmental insults and, as a result, developed a remarkable ability to undergo extensive regeneration. Even under normal circumstances, olfactory sensory neurons (OSN) undergo ongoing and continual regeneration. While the properties of OSNs have been extensively studied in normal and regenerating epithelium, the associated dynamic cellular and molecular changes in non-neuronal olfactory cells are largely unexplored. In this proposal, I will examine the properties of olfactory ensheathing cells (OEC). OECs are a special population of glial cells found exclusively in the olfactory system. They ensheath the axon bundles of OSNs as they project from the olfactory epithelium in the nasal cavity into the olfactory bulb at the front of the brain. Their presence in the olfactory epitheliu and the brain makes OECs a unique type of glial cell that span projections from the peripheral nervous system to the CNS. Their molecular and cellular properties reflect this hybrid role. The purported ability of OECs to promote regeneration has made OECs an attractive therapeutic agent for treating spinal cord injury, stroke, and Parkinson's disease. OECs promote axonal re-growth in vitro and are reported to enhance functional recovery in spinal cord injury models. However, the nature and dynamics of OECs change in response to OSN regeneration has not been studied. Therefore, the goal of this proposal is to study molecular and cellular changes that take place in vivo in OECs during OSN injury, loss, and regeneration. The central hypothesis of this proposal is that the death of olfactory sensory neurons causes critical molecular and cellular changes in olfactory ensheathing cells that encourage successful re- growth of sensory neurons and their axons. Therefore, in this proposal, I will characterize the molecular and cellular responses of OECs during OSN injury and regeneration by monitoring changes in gene expression. Moreover, I will characterize molecular and cellular responses of OSNs due to loss of OECs. The results of the experiments proposed to test this hypothesis will provide us with new insights on the OEC biology, which will lead to improvement of OECs as therapeutic agents for repairing neuronal injury. PUBLIC HEALTH RELEVANCE: In the olfactory system, sensory neurons are closely associated with a cell type called olfactory ensheathing cells (OECs). OECs are a special population of glial cells in the nervous system shown to promote re-growth of certain injured neurons. Therefore, the main aim of this proposal is to gain new insights on the biology of OEC, in order to make improvements to OECs as therapeutic agents for repairing neuronal injury caused by, for example, stroke, physical injury, and Parkinson's disease.